tbuckley/cabot-search huggingface dataset:
<i>TP53</i>gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma
Authors: Yewen Shi, Xiaoyong Ren, Shaolong Cao, Xi Chen, Bo Yuan, Fabio Henrique Brasil da Costa, Alanis E Rodriguez Rosario, Arnoldo Corona, Chieko Michikawa, Ratna Veeramachaneni, Abdullah A Osman, Tongxin Xie, Wenyi Wang, Andrew G Sikora, Jeffrey N Myers, Roberto Rangel
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background TP53 , the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. Somatic TP53 mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role of TP53 gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC. Methods Short hairpin RNA knockdown of mutant p53R172H in syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutant p53R172H . Flow cytometry and multiplex immunofluorescence (mIF) confirmed the role of mutant p53R172H in the TIME. The gene expression of patients with OSCC was analyzed by CIBERSORT and mIF was used to validate the immune landscape at the protein level. Results Mutant p53R172H contributes to a cytokine transcriptome network that inhibits the infiltration of cytotoxic CD8 + T cells and promotes intratumoral recruitment of regulatory T cells and M2 macrophages. Moreover, p53R172H also regulates the spatial distribution of immunocyte populations, and their distribution between central and peripheral intratumoral locations. Interestingly, p53R172H -mutated tumors are infiltrated with CD8 + and CD4 + T cells expressing programmed cell death protein 1, and these tumors responded to immune checkpoint inhibitor and stimulator of interferon gene 1 agonist therapy. CIBERSORT analysis of human OSCC samples revealed associations between immune cell populations and the TP53R175H mutation, which paralleled the findings from our syngeneic mouse tumor model. Conclusions These findings demonstrate that syngeneic tumors bearing the TP53R172H gain-of-function mutation modulate the TIME to evade tumor immunity, leading to tumor progression and decreased survival.
Corrigendum to “Transferrin-guided intelligent nanovesicles augment the targetability and potency of clinical PLK1 inhibitor to acute myeloid leukemia” [Bioact. Mater. 21 (March 2023) 499–510]
Authors: Yifeng Xia, Jingnan An, Jiaying Li, Wenxing Gu, Yifan Zhang, Songsong Zhao, Cenzhu Zhao, Yang Xu, Bin Li, Zhiyuan Zhong, Fenghua Meng
Journal: Bioactive Materials (2023)

[This corrects the article DOI: 10.1016/j.bioactmat.2022.08.032.].
Safety and efficacy of mirikizumab versus secukinumab and placebo in the treatment of moderate-to-severe plaque psoriasis (OASIS-2): a phase 3, multicentre, randomised, double-blind study
Authors: Kim Papp, Richard B Warren, Lawrence Green, Kristian Reich, Richard G Langley, Carle Paul, Akihiko Asahina, Lynne Johnson, Vipin Arora, Olawale Osuntokun, Mark Lebwohl
Journal: The Lancet Rheumatology (2023)
Global comment on the use of hydroxychloroquine during the periconception period and pregnancy in women with autoimmune diseases
Authors: Karen Schreiber, Ian Giles, Nathalie Costedoat-Chalumeau, Catherine Nelson-Piercy, Radboud Jem Dolhain, Marta Mosca, Frauke Förger, Rebecca Fischer-Betz, Anna Molto, Angela Tincani, Elisabeth Pasquier, Benoit Marin, Elisabeth Elefant, Jane Salmon, Bonnie L Bermas, Lisa Sammaritano, Megan E B Clowse, Christina Chambers, Jill Buyon, Saori Abe Inoue, Nancy Agmon-Levin, Silvia Aguilera, Samar Al Emadi, Jeanette Andersen, Danieli Andrade, Aleksandra Antovic, Laurent Arnaud, Alice Ashouri Christiansen, Tadej Avcin, Sara Badreh-Wirström, George Bertsias, Ilaria Bini, Anca Bobirca, Ware Branch, Antonio Brucato, Irene Bultink, Susanna Capela, Irene Cecchi, Ricard Cervera, Cecilia Chighizola, Claudia Cobilinschi, Maria Jose Cuadrado, Dzifa Dey, Oseme Etomi, Gerard Espinosa, Julia Flint, João-Eurico Fonseca, Ruth Fritsch-Stork, Maria Gerosa, Bente Glintborg, Carina Gøtestam Skorpen, Bethan Goulden, Christine Graversgaard, Iva Gunnarsson, Latika Gupta, Merete Hetland, Ken Hodson, Beverley J Hunt, David Isenberg, Søren Jacobsen, Munther Khamashta, Roger Levy, Louise Linde, Jacob Lykke, Yvette Meissner, Louise Moore, Eric Morand, Sandra Navarra, Daniela Opris-Belinski, Monika Østensen, Hiroki Ozawa, Luis Fernando Perez-Garcia, Michelle Petri, Guillermo J Pons-Estel, Massimo Radin, Luigi Raio, Amihai Rottenstreich, Guillermo Ruiz-Irastorza, Slađana Rumpl Tunjić, Marite Rygg, Savino Sciascia, Anja Strangfeld, Elisabet Svenungsson, Maria Tektonidou, Anne Troldborg, Evelyne Vinet, Jelena Vojinovic, Anne Voss, Marianne Wallenius, Laura Andreoli
Journal: The Lancet Rheumatology (2023)
Mining the contribution of intensive care clinical course to outcome after traumatic brain injury
Authors: Shubhayu Bhattacharyay, Pier Francesco Caruso, Cecilia Åkerlund, Lindsay Wilson, Robert D. Stevens, David K. Menon, Ewout W. Steyerberg, David W. Nelson, Ari Ercole
Journal: npj Digital Medicine (2023)

Existing methods to characterise the evolving condition of traumatic brain injury (TBI) patients in the intensive care unit (ICU) do not capture the context necessary for individualising treatment. Here, we integrate all heterogenous data stored in medical records (1166 pre-ICU and ICU variables) to model the individualised contribution of clinical course to 6-month functional outcome on the Glasgow Outcome Scale -Extended (GOSE). On a prospective cohort (n = 1550, 65 centres) of TBI patients, we train recurrent neural network models to map a token-embedded time series representation of all variables (including missing values) to an ordinal GOSE prognosis every 2 h. The full range of variables explains up to 52% (95% CI: 50-54%) of the ordinal variance in functional outcome. Up to 91% (95% CI: 90-91%) of this explanation is derived from pre-ICU and admission information (i.e., static variables). Information collected in the ICU (i.e., dynamic variables) increases explanation (by up to 5% [95% CI: 4-6%]), though not enough to counter poorer overall performance in longer-stay (>5.75 days) patients. Highest-contributing variables include physician-based prognoses, CT features, and markers of neurological function. Whilst static information currently accounts for the majority of functional outcome explanation after TBI, data-driven analysis highlights investigative avenues to improve the dynamic characterisation of longer-stay patients. Moreover, our modelling strategy proves useful for converting large patient records into interpretable time series with missing data integration and minimal processing.
Trends in Well-Being Among Youth in Australia, 2017-2022
Authors: Dorothea Dumuid, Ben Singh, Jacinta Brinsley, Rosa Virgara, Rachel G. Curtis, Sally Brinkman, Carol A. Maher
Journal: JAMA Network Open (2023)

Importance Little is known about temporal trends in children’s well-being and how the COVID-19 pandemic may have influenced the well-being of young Australians. Certain demographic groups may be more vulnerable to experiencing declines in well-being. Objective To examine well-being trends over 6 consecutive years among South Australian students and explore the influence of sociodemographic characteristics. Design, Setting, and Participants Longitudinal analyses of annual (2017 to 2022) cross-sectional data of students in grades 4 through 9 (n = 40 392 to 56 897 per year) attending South Australian government schools from the Well-being and Engagement Collection (WEC) census. Exposures Calendar year (2017-2022) and sociodemographic characteristics (sex, school grade, parental education, language spoken at home, residential region) from school enrollment records. Main Outcomes and Measures Students self-reported life satisfaction, optimism, happiness, cognitive engagement, emotional regulation, perseverance, worry, and sadness. Results Over 6 years (2017 to 2022), a total of 119 033 students (mean [SD] age, 12.1 y; 51.4% male) participated in this study. Most well-being measures declined over time, with consistent worsening of well-being from 2020 onward. For example, compared with 2017, sadness was 0.26 (95% CI, 0.25-0.27) points higher in 2020 (standardized mean difference [SMD], 0.27) and remained elevated by more than 0.26 points (SMD, 0.27) in 2021 and 2022. At almost every time point, greatest well-being was reported by students of male sex (except cognitive engagement and perseverance), in earlier school grades, with highest parental education, speaking a language other than English at home, and residing in outer regional and remote settings (for satisfaction, optimism, and emotional regulation). Sociodemographic differences in well-being were generally consistent over time; however, sex differences widened from 2020 for all indicators except cognitive engagement and perseverance. For example, between 2017 and 2022, sadness increased by 0.27 (95% CI, 0.25-0.29) more points among females than males (SMD, 0.28). Conclusions and Relevance In this longitudinal analysis of annual census data, there were downward trends in students’ well-being, especially since 2020. The largest sociodemographic disparities were observed for students of female sex, those in later school grades, and those with lowest parental education. Urgent and equitable support for the well-being of all young people, particularly those facing disparity, is imperative.
Understanding the Facets of Emulating Randomized Clinical Trials
Authors: Sukrit Narula, Ilias Nikolakopoulos
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Understanding the Facets of Emulating Randomized Clinical Trials
Authors: Nicholas A. Bosch, Anica C. Law, Allan J. Walkey
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Scaffold‐Free Tracheal Engineering via a Modular Strategy Based on Cartilage and Epithelium Sheets
Authors: Minglei Yang, Jiafei Chen, Yi Chen, Weikang Lin, Hai Tang, Ziwen Fan, Long Wang, Yunlang She, Feng Jin, Lei Zhang, Weiyan Sun, Chang Chen
Journal: Advanced Healthcare Materials (2023)

Adv. Healthcare Mater. 2023, 12, 2202022 https://doi.org/10.1002/adhm.202202022 In the originally published version of this article, the author Feng Jin's affiliation is incorrectly listed as “Shandong Province Chest Hospital, Shandong 250011, China”. This is incorrect. The correct affiliation should be “Shandong Key Laboratory of Infectious Respiratory Diseases, Shandong Public Health Clinical Center Affiliated to Shandong University, Shandong 250013, China”. This error does not affect the conclusions of this article. The authors apologize for any inconvenience caused.
Network analysis identifies strain-dependent response to tau and tau seeding-associated genes
Authors: Dominic J. Acri, Yanwen You, Mason D. Tate, Hande Karahan, Pablo Martinez, Brianne McCord, A. Daniel Sharify, Sutha John, Byungwook Kim, Luke C. Dabin, Stéphanie Philtjens, H.R. Sagara Wijeratne, Tyler J. McCray, Daniel C. Smith, Stephanie J. Bissel, Bruce T. Lamb, Cristian A. Lasagna-Reeves, Jungsu Kim
Journal: The Journal of Experimental Medicine (2023)

Previous research demonstrated that genetic heterogeneity is a critical factor in modeling amyloid accumulation and other Alzheimer’s disease phenotypes. However, it is unknown what mechanisms underlie these effects of genetic background on modeling tau aggregate-driven pathogenicity. In this study, we induced tau aggregation in wild-derived mice by expressing MAPT. To investigate the effect of genetic background on the action of tau aggregates, we performed RNA sequencing with brains of C57BL/6J, CAST/EiJ, PWK/PhJ, and WSB/EiJ mice (n = 64) and determined core transcriptional signature conserved in all genetic backgrounds and signature unique to wild-derived backgrounds. By measuring tau seeding activity using the cortex, we identified 19 key genes associated with tau seeding and amyloid response. Interestingly, microglial pathways were strongly associated with tau seeding activity in CAST/EiJ and PWK/PhJ backgrounds. Collectively, our study demonstrates that mouse genetic context affects tau-mediated alteration of transcriptome and tau seeding. The gene modules associated with tau seeding provide an important resource to better model tauopathy.
Marginal zone lymphoma: 2023 update on diagnosis and management
Authors: Chan Y. Cheah, John F. Seymour
Journal: American Journal of Hematology (2023)

Marginal zone lymphomas (MZL) are collectively the second most common type of indolent lymphoma.Three subtypes of MZL are recognized: splenic, extranodal, and nodal. The diagnosis is secured following biopsy of an involved nodal or extranodal site demonstrating a clonal B-cell infiltrate with CD5 and CD10 negative immunophenotype most common. Some cases will features IgM paraprotein, but MYD88 L256P mutations are less frequent than in Waldenstrom macroglobulinemia. Prognostication Several prognostic models have been developed, including the MALT-IPI and the MZL-IPI. The latter is broadly applicable across MZL subtypes and incorporates elevated serum LDH, anemia, lymphopenia, thrombocytopenia and nodal or disseminated subtypes as independent predictors of outcome.We discuss suggested approach to therapy for both early and advanced-stage disease, with reference to chemo-immunotherapy, radiotherapy, and emerging treatments in relapsed/refractory disease such as BTK inhibitors.
Effect of Vitamin D Supplements on Relapse or Death in a p53-Immunoreactive Subgroup With Digestive Tract Cancer
Authors: Kazuki Kanno, Taisuke Akutsu, Hironori Ohdaira, Yutaka Suzuki, Mitsuyoshi Urashima
Journal: JAMA Network Open (2023)

Recent meta-analyses of randomized clinical trials found that daily vitamin D3 supplementation had beneficial effects on cancer mortality, although the results are still controversial.To examine whether vitamin D supplementation reduces the risk of relapse or death in a supgroup of patients with digestive tract cancer who were p53 immunoreactive.This was a post hoc subgroup analysis of the AMATERASU randomized, double-blind, placebo-controlled clinical trial. This trial included patients at a single university hospital in Japan with digestive tract cancers between January 2010 and February 2018 followed up for a median (IQR) of 3.5 (2.5-5.3) years to compare the effects of vitamin D supplementation with placebo and was reported in 2019. Patients from among 417 participants in the AMATERASU trial whose residual serum samples were available were included. Data were analyzed from October 20 to November 24, 2022.Vitamin D3 (2000 IU/d) supplementation or placebo.The primary outcome was 5-year relapse or death. The subgroup of patients who were p53 immunoreactive was defined by positivity for anti-p53 antibodies in serum and nuclear accumulation of p53 oncosuppressor protein in more than 99% of cancer cells, which is considered a biomarker for p53 missense mutations. Anti-p53 antibody levels were measured using chemiluminescent enzyme immune assay. Immunohistochemical staining data of p53 protein in cancer tissue in pathologic specimens were obtained from a previous study and divided into 4 grades.Among 392 patients with digestive tract cancer (mean [SD] age, 66 [10.7] years; 260 males [66.3%]), there were 37 patients with esophageal cancer (9.4%), 170 patients with gastric cancer (43.4%), 2 patients with small bowel cancer (0.5%), and 183 patients with colorectal cancer (46.7%). Serum anti-p53 antibody was detectable in 142 patients (36.2%), and p53-immunohistochemistry grade showed a positive association with serum anti-p53 antibody levels (coefficient = 0.19; P < .001). In the p53-immunoreactive subgroup (80 patients), relapse or death occurred in 9 of 54 patients (16.7%) in the vitamin D group and 14 of 26 patients (53.8%) in the placebo group; 5-year relapse-free survival (RFS) was significantly higher in the vitamin D group (13 patients [80.9%]) than the placebo group (1 patient [30.6%]; hazard ratio [HR], 0.27; 95% CI, 0.11-0.61; P = .002). This was significantly different from 272 patients in the non-p53 immunoreactive subgroup, in which vitamin D had no effect on 5-year RFS (vitamin D: 35 of 158 patients [22.2%] vs placebo: 24 of 114 patients [21.1%]; HR, 1.09; 95% CI, 0.65-1.84) (P for interaction = .005).This study found that vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients with digestive tract cancer who were p53 immunoreactive.Identifier: UMIN000001977.
Preexposure Prophylaxis to Prevent Acquisition of HIV
Authors: Michael J. Barry, Wanda K. Nicholson, Michael Silverstein, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Katrina E. Donahue, Carlos Roberto Jaén, Marti Kubik, Li Li, Gbenga Ogedegbe, Goutham Rao, John M. Ruiz, James J. Stevermer, Joel Tsevat, Sandra Millon Underwood, John B. Wong
Journal: JAMA (2023)

Importance An estimated 1.2 million persons in the US currently have HIV, and more than 760 000 persons have died of complications related to HIV since the first cases were reported in 1981. Although treatable, HIV is not curable and has significant health consequences. Therefore, effective strategies to prevent HIV are an important public health and clinical priority. Objective The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of preexposure prophylaxis with antiretroviral therapy for the prevention of HIV acquisition, and the diagnostic accuracy of risk assessment tools to identify persons at increased risk of HIV acquisition. Population Adolescents and adults who do not have HIV and are at increased risk of HIV. Evidence Assessment The USPSTF concludes with high certainty that there is a substantial net benefit from the use of effective antiretroviral therapy to reduce the risk of acquisition of HIV in persons at increased risk of acquiring HIV. Recommendation The USPSTF recommends that clinicians prescribe preexposure prophylaxis using effective antiretroviral therapy to persons at increased risk of HIV acquisition to decrease the risk of acquiring HIV. (A recommendation)
Transition to Reusable Surgical Gowns at a Hospital System
Authors: Ava Yap, Kaiyi Wang, John Cornejo, Evan Chen, Logan Pierce, Elizabeth Wick, Seema Gandhi
Journal: JAMA Network Open (2023)

This quality improvement study investigates the feasibility of transitioning back to reusable surgical gowns at a US tertiary hospital system and projected corresponding cost savings and solid waste reduction.
Coordinated Care for Optimization of Cardiovascular Preventive Therapies in Patients With Diabetes—Reply
Authors: Neha Jadeja Pagidipati, Christopher B. Granger, Adam Nelson
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal